Alzheimer's disease is a growing medical problem afflicting 5% of the over-65 population in the US. Despite its prevalence, neither positive diagnoses nor efficacious treatments exist. Definitive diagnosis is made on autopsy using the histopathological hallmarks of the disease - fibrillar amyloid protein which is deposited extracellularly as plaque cores and as cerebrovasculature amyloid. These structures occur at approximately 1000-fol greater frequency than in a normal aged brain. The major core protein of amyloid fibrils has been purified and recently the cDNA cloned. The aim of phase I is to develop nucleic acid and antibody reagents to the core protein which can be utilized to build a biochemica diagnostic for Alzheimer's disease. Using the cDNA sequence, core protein-specific antibodies will be generated either from synthetic peptides or from proteins expressed by recombinant methods. In phase II sera will be screened with the antibodies and the nucleic acid probes to assess qualitative and/or quantitative differences reflecting the disease state. Such differences would then be developed into a positive diagnostic for Alzheimer's disease.